Investigating the generation of hydrogen sulfide from the phosphonamidodithioate slow-release donor GYY4137

被引：51

作者：

Alexander, Benjamin E. ^{[1
]}

Coles, Simon J. ^{[2
]}

Fox, Bridget C. ^{[3
]}

Khan, Tahmina F. ^{[1
]}

Maliszewski, Joseph ^{[1
]}

Perry, Alexis ^{[1
]}

Pitak, Mateusz B. ^{[2
]}

Whiteman, Matthew ^{[3
]}

Wood, Mark E. ^{[1
]}

机构：

[1] Univ Exeter, Coll Life & Environm Sci, Biosci, Exeter EX4 4QD, Devon, England

[2] Univ Southampton, EPSRC UK Natl Crystallog Serv, Chem, Southampton SO17 1BJ, Hants, England

[3] Univ Exeter, Sch Med, Exeter EX1 2LU, Devon, England

来源：

MEDCHEMCOMM | 2015年 / 6卷 / 09期

关键词：

H2S; CHEMISTRY; CELLS;

D O I：

10.1039/c5md00170f

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A combination of NMR spectroscopy, mass spectrometry and chemical synthesis was used to elucidate the two-step hydrolytic decomposition pathway of the slow-release hydrogen sulfide (H2S) donor GYY4137 and the key decomposition product was also prepared by an independent synthetic route. The (dichloromethane-free) sodium salt of the phosphonamidodithioate GYY4137 was also produced as a pharmaceutically more acceptable salt. In contrast with GYY4137 and its sodium salt, the decomposition product did not generate H2S or exert cytoprotective or anti-inflammatory effects in oxidatively stressed human Jurkat T-cells and LPS-treated murine RAW264.7 macrophages. The decomposition product represents a useful control compound for determining the biological and pharmacological effects of H2S generated from GYY4137.

引用

页码：1649 / 1655

页数：7